Edward Thomas Ryan
Professor

Edward Thomas Ryan

Professor in the Department of Immunology and Infectious Diseases

Immunology and Infectious Diseases

etryan@partners.org

Other Positions

Professor of Medicine

Medicine

Massachusetts General Hospital


Overview

Edward T. Ryan, M.D. is the Director of Global Infectious Diseases, Massachusetts General Hospital, Boston, MA, Professor of Medicine, Harvard Medical School, and Professor of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health. Dr. Ryan received his Bachelor's degree in Biochemical Sciences from Princeton University, and a Doctorate in Medicine from Harvard University. He performed medical residency and fellowship training in infectious diseases at the Massachusetts General Hospital. Dr. Ryan received additional training in tropical medicine and infectious diseases at the London School of Hygiene & Tropical Medicine, was a Fellow in Human Rights & Medicine, Columbia University, and was an International Fellow, International Centre for Diarrhoeal Disease Research (ICDDR, B), Dhaka, Bangladesh.

Dr. Ryan has served on expert and advisory committees for the Institute of Medicine-National Academy of Sciences, U.S. Centers for Disease Control & Prevention, chaired the Clinical Research and Field Studies of Infectious Diseases Study section of the US NIH from 2006-2008, chaired the Standards and Treatment Guidelines Committee of the American Society of Tropical Medicine & Hygiene (ASTMH) 2010-2018, and served as ASTMH President from 2009-2010. Dr. Ryan has been elected to Fellowship of the American College of Physicians, the Infectious Diseases Society of America, the American Society of Tropical Medicine and Hygiene, and the American Academy of Microbiology. Dr Ryan has published over 300 peer-reviewed journal articles and book chapters on global infectious diseases, enteric infections, vaccines, and tropical medicine. Dr. Ryan is a Senior Editor of Hunter's Tropical Medicine, and a Medical Editor of the Centers for Disease Control and Prevention Yellow Book.

Research:

Our research focuses on host-bacterial pathogen interactions and immune responses, with a particular focus on enteric infections and the development of vaccines protective against enteric infections, and development of diagnostic assays. Specific focus areas include Vibrio cholerae, the cause of cholera; Salmonella enterica, the causes of typhoid and paratyphoid fever; and Shigella spp, the cause of dysentery. We work in collaborative efforts with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka Bangladesh (ICDDR,B), as well as with colleagues in Nepal, Pakistan, Haiti, and South Sudan.

Immune responses during cholera

In a collaborative effort with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (ICDDR,B), we are evaluating immune responses in humans infected with Vibrio cholerae, the cause of cholera. V. cholerae is endemic in over 50 countries, infects approximately 3-5 million individuals globally, and results in the death of approximately 100,000 individuals each year. Individuals most affected by cholera are those most impoverished, especially those lacking safe water and sanitary facilities, as well as individuals displaced by war, famine, disasters, and conflict. Cholera can be explosively epidemic, and the global burden of cholera may well increase with climate change, severe weather events, and increasing urbanization. V. cholerae is a human-restricted infection, and current cholera vaccines provide relatively short-term protection against disease. The mediators of protective immunity against cholera are poorly understood. To address this, we are applying a number of high throughput and platform technologies to assess innate and adaptive immune responses in humans with cholera and their household contacts, stratifying responses in the latter by subsequent protection from disease, and comparing responses in the former to those that occur in recipients of current cholera vaccines. The goal of these studies is to identify the mediators of protection against cholera, in order to advance improved prevention strategies, as well as to advance vaccine development and deployment.

Host-pathogen interactions during typhoid fever

In a collaborative effort with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (ICDDR,B), we are evaluating host-pathogen interactions and immune responses in humans infected with Salmonella enterica serotype Typhi (the cause of typhoid fever) and S. Paratyphi (the cause of paratyphoid fever). Together, S. Typhi and S. Paratyphi cause approximately 20 million cases of enteric fever world-wide, resulting in approximately 200,000 deaths each year. Most of these deaths occur in impoverished children and young adults. Although usually caused by S. Typhi, one in four cases of enteric fever is caused by S. Paratyphi in many areas of the world. S. Typhi and S. Paratyphi are particularly common among urban residents in informal settlements and slums, although any individual lacking safe water and sanitary facilities is at risk of infection. Vaccines against S. Typhi provide only 50-60% protection against disease for 2-5 years, and, at present, there is no commercially available vaccine against S. Paratyphi. There is also no good point-of-care test to diagnose individuals with enteric fever, and S. Typhi and S. Paratyphi are becoming increasingly resistant to antimicrobial agents.To address this, we are evaluating host-pathogen interactions directly in humans infected with S. Typhi and S. Paratyphi. We are applying a number of technologies to evaluate innate and adaptive immune responses directly in humans infected with S. Typhi and S. Paratyphi in Bangladesh, and we are evaluating bacterial responses in humans during these human-restricted infections. The goal of these studies is to develop improved diagnostic assays, antimicrobial agents, and preventative strategies against these infections.

Immunization approaches for enteric infection

A fundamental challenge facing many enteric and mucosal vaccines is their inability to induce long-term protective immunity. Many of these vaccines may not be prominent inducers of memory cells, which play critical roles in mediating long-term protection against disease. Using our analysis of memory B and T cell induction during wild-type human enteric infection in Bangladesh, we are evaluating the ability of a number of vaccination approaches and strategies to induce long-term memory responses protective against mucosal and enteric infections, including development of enteric conjugate vaccines, and analysis of oral-transcutaneous prime-boosting approaches.

Global TravEpinet (GTEN)

To extend our analysis of infections associated with living in, traveling through, or immigrating from resource-limited areas, we also work with the U.S. Centers for Disease Control and Prevention through the GTEN (Global TravEpiNet; Global Travelers' Epidemiology Network) Program. GTEN's mission is to advance the health of American residents who travel internationally, as well as to lessen the likelihood of disease importation into home communities. GTEN-relate resources are available at Heading Home Healthy. Through this program, we have been able to address COVID-19, an illness introduced into U.S. populations through travel. Our efforts have focused on understanding diagnostic assays and transmission dynamics to assist in control measures. We have assessed immune responses during SARS-CoV-2 infection, including duration and cross reactivity with other coronaviridae, characterized immune responses during naturally acquired disease to inform vaccine development, and phylogenetically typed viral strains to assess introduction and transmission of SARS-CoV-2 at population levels.


Bibliography

An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates.

Zabaleta N, Dai W, Bhatt U, Hérate C, Maisonnasse P, Chichester JA, Sanmiguel J, Estelien R, Michalson KT, Diop C, Maciorowski D, Dereuddre-Bosquet N, Cavarelli M, Gallouët AS, Naninck T, Kahlaoui N, Lemaitre J, Qi W, Hudspeth E, Cucalon A, Dyer CD, Pampena MB, Knox JJ, LaRocque RC, Charles RC, Li D, Kim M, Sheridan A, Storm N, Johnson RI, Feldman J, Hauser BM, Contreras V, Marlin R, Tsong Fang RH, Chapon C, van der Werf S, Zinn E, Ryan A, Kobayashi DT, Chauhan R, McGlynn M, Ryan ET, Schmidt AG, Price B, Honko A, Griffiths A, Yaghmour S, Hodge R, Betts MR, Freeman MW, Wilson JM, Le Grand R, Vandenberghe LH.

Cell Host Microbe. 2021 09 08. 29(9):1437-1453.e8. PMID: 34428428

Correction: Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh.

Aktar A, Rahman MA, Afrin S, Akter A, Uddin T, Yasmin T, Sami MIN, Dash P, Jahan SR, Chowdhury F, Khan AI, LaRocque RC, Charles RC, Bhuiyan TR, Mandlik A, Kelly M, Kovác P, Xu P, Calderwood SB, Harris JB, Qadri F, Ryan ET.

PLoS Negl Trop Dis. 2021 Jul. 15(7):e0009616. PMID: 34280200

Defining Polysaccharide-Specific Antibody Targets against Vibrio cholerae O139 in Humans following O139 Cholera and following Vaccination with a Commercial Bivalent Oral Cholera Vaccine, and Evaluation of Conjugate Vaccines Targeting O139.

Kamruzzaman M, Kelly M, Charles RC, Harris JB, Calderwood SB, Akter A, Biswas R, Kaisar MH, Bhuiyan TR, Ivers LC, Ternier R, Jerome JG, Pfister HB, Lu X, Soliman SE, Ruttens B, Saksena R, Mecárová J, Cížová A, Qadri F, Bystrický S, Kovác P, Xu P, Ryan ET.

mSphere. 2021 08 25. 6(4):e0011421. PMID: 34232076

Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: a guide and case study in setting up an emergency-use, laboratory-developed molecular microbiological assay.

Anahtar MN, Shaw BM, Slater D, Byrne EH, Botti-Lodovico Y, Adams G, Schaffner SF, Eversley J, McGrath GEG, Gogakos T, Lennerz J, Marble HD, Ritterhouse LL, Batten JM, Georgantas NZ, Pellerin R, Signorelli S, Thierauf J, Kemball M, Happi C, Grant DS, Ndiaye D, Siddle KJ, Mehta SB, Harris JB, Ryan ET, Pierce VM, LaRocque RC, Lemieux JE, Sabeti PC, Rosenberg ES, Branda JA, Turbett SE.

J Clin Pathol. 2021 Aug. 74(8):496-503. PMID: 34049977